Linda T. Kohn

To Err is Human

A process for the preparation of R alpha -cyclopentenoids and then R alpha , R omega -cyclopentanoids is described. The process involves the reaction of a compound of the formula where X is halo, particularly Br or I and P is a protecting group with an alkylborane to produce the R alpha -cyclopentenone. The R alpha -cyclopentenone is reacted with a R omega cuprate to produce the R alpha , R omega -cyclopentenoid. The process is used for the preparation of prostaglandins which are known pharmaceutically active compounds.

Genomic analysis of the necrotrophic fungal pathogens Sclerotinia sclerotiorum and Botrytis cinerea.

Sclerotinia sclerotiorum and Botrytis cinerea are closely related necrotrophic plant pathogenic fungi notable for their wide host ranges and environmental persistence. These attributes have made these species models for understanding the complexity of necrotrophic, broad host-range pathogenicity. Despite their similarities, the two species differ in mating behaviour and the ability to produce asexual spores. We have sequenced the genomes of one strain of S. sclerotiorum and two strains of B. cinerea. The comparative analysis of these genomes relative to one another and to other sequenced fungal genomes is provided here. Their 38–39 Mb genomes include 11,860–14,270 predicted genes, which share 83% amino acid identity on average between the two species. We have mapped the S. sclerotiorum assembly to 16 chromosomes and found large-scale co-linearity with the B. cinerea genomes. Seven percent of the S. sclerotiorum genome comprises transposable elements compared to <1% of B. cinerea. The arsenal of genes associated with necrotrophic processes is similar between the species, including genes involved in plant cell wall degradation and oxalic acid production. Analysis of secondary metabolism gene clusters revealed an expansion in number and diversity of B. cinerea–specific secondary metabolites relative to S. sclerotiorum. The potential diversity in secondary metabolism might be involved in adaptation to specific ecological niches. Comparative genome analysis revealed the basis of differing sexual mating compatibility systems between S. sclerotiorum and B. cinerea. The organization of the mating-type loci differs, and their structures provide evidence for the evolution of heterothallism from homothallism. These data shed light on the evolutionary and mechanistic bases of the genetically complex traits of necrotrophic pathogenicity and sexual mating. This resource should facilitate the functional studies designed to better understand what makes these fungi such successful and persistent pathogens of agronomic crops.

2 - Inferring Process from Pattern in Fungal Population Genetics

Our focus in this review is on powerful new methods for determining population patterning over time and space and how from this, the dynamic processes leading to population divergence and speciation can be inferred. We focus on fungal populations, but draw from the wider literature on population genetics, evolutionary statistics, and, of course, phylogeography (see Avise, 2000). We discuss the problems of gene duplication, paralogy, orthology, and deep coalescence as challenges to finding the interface between population divergence and speciation. Our main objective, however, is to guide the reader through the key phylogenetic, nested phylogenetic, coalescent and Bayesian operations with the aid of a set of figures based on a simple, hypothetical dataset of DNA haplotypes. Phylogenetic and compatibility approaches are presented with the goal of not only detecting recombination, but of detecting recombination when it is not widespread throughout a phylogeny. This is a major challenge in fungal systems with substantial asexual reproduction or with significant selfed sexual reproduction in a haploid genome. The key feature here is that recombination can be “localized” in some but not all clades in a phylogeny and that these clades can be identified. From this, contemporary versus historical patterns of recombination can be inferred from a phylogeny. Phylogenetic approaches based on conversion of the phylogeny to a nested hierarchical statistical design are presented for fuller exploration of associations between each nested level of the phylogeny and any variable, such as geographical location, host, or symptom type. The basic operations for both testing for population subdivision based on geographical associations, and for cladistic inference of population processes are presented. Our hypothetical dataset is also used to demonstrate how genealogical relationships and population parameters can be inferred using coalescent and Bayesian methods. The basic principles of these approaches are graphically presented, along with useful references and comments on key assumptions implicit in methods currently available.

Academic Health Centers

Academic Health Centers (AHCs) have a unique challenge in effectively and simultaneously meeting the demands of all three areas of their mission: education, research, and patient care. In particular, AHCs must adapt quickly to the rapidly evolving and complex health care system in order to remain competitive, and their governance structures, leadership, and policies must facilitate such nimbleness. AHCs nationally have struggled to find the most appropriate structure to meet their particular needs, and a number of governance models exist.